Pyridine 4-methylbenzene-1-sulfonate → Azd-8835

HRID 1749045노트

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HRID 1749045 반응식
CC1C=CC(S(O)(=O)=O)=CC=1.N1C=CC=CC=1.[NH2:18][C:19]1[N:20]=[CH:21][C:22]([C:34]2[N:38]([CH2:39][CH3:40])[N:37]=[C:36]([CH:41]3[CH2:46][CH2:45][N:44]([C:47](=[O:57])[CH2:48][CH2:49][O:50]C4CCCCO4)[CH2:43][CH2:42]3)[N:35]=2)=[N:23][C:24]=1[C:25]1[O:26][C:27]([C:30]([CH3:33])([CH3:32])[CH3:31])=[N:28][N:29]=1>CO>[NH2:18][C:19]1[N:20]=[CH:21][C:22]([C:34]2[N:38]([CH2:39][CH3:40])[N:37]=[C:36]([CH:41]3[CH2:42][CH2:43][N:44]([C:47](=[O:57])[CH2:48][CH2:49][OH:50])[CH2:45][CH2:46]3)[N:35]=2)=[N:23][C:24]=1[C:25]1[O:26][C:27]([C:30]([CH3:33])([CH3:31])[CH3:32])=[N:28][N:29]=1

참가 물질

4

반응물 2

HCID 161440Pyridine 4-methylbenzene-1-sulfonateHCID 867276661-(4-(5-(5-amino-6-(5-tert-butyl-1,3,4-oxadiazol-2-yl)pyrazin-2-yl)-1-ethyl-1H-1,2,4-triazol-3-yl)piperidin-1-yl)-3-(tetrahydro-2H-pyran-2-yloxy)propan-1-one

생성물 1

HCID 76685059Azd-8835수율 85%

시약·촉매·용매 1

HCID 887Methanol용매

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온도
60 °C

실험 절차

Pyridine 4-methylbenzenesulfonate (11.62 g, 46.24 mmol) was added to a suspension of 1-(4-(5-(5-amino-6-(5-tert-butyl-1,3,4-oxadiazol-2-yl)pyrazin-2-yl)-1-ethyl-1H-1,2,4-triazol-3-yl)piperidin-1-yl)-3-(tetrahydro-2H-pyran-2-yloxy)propan-1-one (128 g, 231.19 mmol) in methanol (1 L) under nitrogen. The mixture was stirred at 60° C. for 1.5 hours. The mixture was soluble after 5 minutes. The mixture was held at 50° C. overnight during which time a precipitate formed. The solid material was isolated by filtration and washed with water and acetonitrile. This material still contained minor impurities from the previous stage and required further purification. The material was dissolved in dichloromethane and purified by flash chromatography on silica gel (0% methanol/DCM to 10% methanol/DCM). The desired product, 1-(4-(5-(5-amino-6-(5-tert-butyl-1,3,4-oxadiazol-2-yl)pyrazin-2-yl)-1-ethyl-1H-1,2,4-triazol-3-yl)piperidin-1-yl)-3-hydroxypropan-1-one (Reference Example 1) (92 g, 85%), was thus isolated as a cream solid (Form A): 1H NMR Spectrum: (DMSO-d6) 1.4-1.51 (12H, m), 1.51-1.78 (2H, m), 1.89-2.05 (2H, n), 72-2.86 (1H, m), 2.91-3.05 (1H, m), 3.12-3.24 (1H, m), 3.64 (2H, q), 3.83-4.01 (1H, m), 4.29-4.41 (1H, m), 4.47 (1H, t), 4.58 (2H, q), 8.26 (2H, s), 8.85 (1H, s): Mass Spectrum [M+H]+=470.

후처리

  1. waitThe mixture was soluble after 5 minutes
  2. waitThe mixture was held at 50° C. overnight during which time
  3. customa precipitate formed
  4. customThe solid material was isolated by filtration
  5. washwashed with water and acetonitrile
  6. customThis material still contained minor impurities from the previous stage and required further purification
  7. dissolutionThe material was dissolved in dichloromethane
  8. custompurified by flash chromatography on silica gel (0% methanol/DCM to 10% methanol/DCM)

출처 및 근거

ORD 기록
ord-c444e4c9538440e4aec6263ef097a9f7
출처 데이터셋
uspto-grants-2015_10
특허 번호
US09155727B2

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